Monday, December 12, 2016

Naegleria fowleri: A Clinical Race Against Time

by SE

As a medical laboratory technician, I have learned that accuracy and efficiency in laboratory testing are essential virtues for the process of clinical diagnosis. The faster a physician gets results, the faster an effective differential can be performed. This not only leads to quality care for the patient, but can even mean the difference between life and death. As the medical technology industry expands, and the communication network between clinical sites become more efficient, patients have greater chances for survival, even when they are facing some of the most horrifying situations.
The following is a comparison of two case studies involving the same pathogen, Naegleria fowleri. Case One, taken from an article in Clinical Infectious Diseases, involves a four-year-old boy in Louisiana(1). Case Two, taken from an article in PEDIATRICS, involves a twelve-year-old girl in Arkansas(2). Both cases begin in the middle of July, 2013.

The symptoms:
In the case of the four-year-old boy, symptoms began to present as vomiting and headache with a fever of 104 degrees F. Two staring spells occurred in which the boy was non-responsive for several seconds at a time before returning to normal. After the second occurrence, the boy was brought into the New Orleans emergency department. There, a third occurrence of staring was observed. The boy’s vitals were all within normal ranges. His headaches persisted until day three, when he began to suffer hypertension, slowed heartbeat, and multiple seizures. (1)
For the case of the twelve-year-old girl, symptoms also presented as severe headaches over two days. On the second say, a fever of 103 degrees F also presented, along with nausea and vomiting. She was admitted to the Arkansas Children’s Hospital where her condition worsened. On day three she developed right-sided abducens nerve palsy -the inability to turn her eye outward. (2)
According to the CDC, early symptoms of infection by Naegleria fowleri include severe frontal headaches, fever, nausea and vomiting. This was seen in both cases above and unfortunately, are not very specific indications as to what may be the cause. These symptoms appear about five days after exposure to the ameba and are likely attributed to immune response to the infection. Late symptoms occur only days after the first set of symptoms present. These new symptoms include stiff neck, seizures, altered mental status, and eventually coma and death. Naegleria fowleri is a free-living ameba that lives in warm freshwater, including lakes, swamps, and streams. It is motile in this stage and feeds on bacteria in the water. When it comes in contact with a human through their nose, it will make it’s way toward the brain. Here, it causes Primary meningoencephalitis(PAM) as it feeds on brain tissue. (3)

The Clinical Development:
                  During the boy’s second day of symptomatic presentation, his CT scan presented normal, while both his blood and cerebral spinal fluid(CSF) showed elevated levels of white blood cells(WBC). A brain scan on day three showed signs of edema. By day four, there was no longer any electro-cerebral activity. (1)
                  In the girl’s case, she too had a normal CT scan upon first arrival at the hospital. Like the boy, her white blood cells were also elevated. The CSF from her lumbar puncture was examined for infection, where the ameba Naegleria was identified. A sample was sent to the CDC for further confirmation. On day two, she developed intracranial pressure due to edema, which worsened by day three. (2)
                  Infection with Naegleria fowleri is very dangerous and it can be difficult to diagnose due the non-specific presentation of symptoms. Generally, observation of ameba in the CSF is the fastest and only current way to rule out similar possibilities such as bacterial meningitis. Confirmation through a reference lab, such as the CDC, helps to focus treatment as speed seems to be key for a better prognosis. The alternative way to confirm infection by Naegleria fowleri has traditionally been by autopsy after the patient has passed. Since 1962, 132 cases of PAM by Naegleria fowleri have been recorded with only 4 survivors across North America. (2)

The Treatment:
                  The boy was first given acetaminophen by the mother when symptoms first developed, which had no effect. At the hospital, he was administered Vancomycin and ceftriaxone to treat any possible bacterial meningitis. After seeing elevated WBC count in the CSF, piperacillintazobactam and acyclovir were administered. When signs of edema in the brain showed on day three, the boy was put in an induced coma and treated with hyperosmolar therapy to reduce pressure in the brain. Unfortunately, symptoms worsened, and by day five the family chose to remove life support. (1)
                  When the laboratory in Arkansas reported possible Naegleria infection in the girl’s CSF, she was placed on amphotericin, fluconazole, rifampin, azithromycin, and dexamethasone. On her second day of hospitalization, the CDC confirmed the infection of Naegleria fowleri and she was treated with hyperosmolar therapy and induced hypothermia. She was also started on miltefosine. The treatment regimen was sustained for nearly a week, while daily CSF monitoring showed a steady reduction in infectious load. The girl recovered from edema after two weeks and finished the rehabilitation and antibacterial treatment by day fifty-five. She was able to return to school soon after. (2)
According to an article by Travis Heggie, Naegleria fowleri has been found in places all around the globe, including Japan, Australia, England, and Italy(4). As a free-living ameba, it is able to live in the soil, although it prefers warm liquid environments. Most often, infection occurs when someone goes swimming and inhales the contaminated water. Symptoms may not arise for up to nine days after infection, leading investigators to search multiple habitats the individual may have visited since. In the case of the boy in Louisiana, investigators determined that contamination came from the tap water, likely due to poor conditions post hurricane Katrina(1).
The CDC’s recommended treatment for Naegleria fowleri infection includes a combination of antimicrobials and aggressive management of acute symptoms. The most important thing to increase odds of survivability seems to be the speed of diagnosis, leading to immediate treatment. Naegleria fowleri acts fast, and the damage it causes is quickly fatal. The CDC now holds a stock of miltefosine as an investigational drug to help fight off infection. Meanwhile, fluid buildup and inflammation in the brain needs to be reduced through hyperosmolar and hypothermic therapies. These therapies pull the fluid back into circulation, away from the brain, and slow the progression of the ameba until the medication and the body’s immune system can fight back. After the infection clears, the body still needs time to recover from the trauma, often requiring physical therapy. (3)

1)    Cope, Jennifer R. et al. “The First Association of a Primary Amebic Meningoencephalitis Death with Culturable Naegleria Fowleri in Tap Water from a US Treated Public Drinking Water System.” Clinical Infectious Diseases 60 (2015): e36–e42. Web.
2)    Linam, W M et al. “Successful Treatment of an Adolescent with Naegleria Fowleri Primary Amebic Meningoencephalitis.” Pediatrics 135.3 (2015): e744–8. Web.
3)    “Naegleria Fowleri — Primary Amebic Meningoencephalitis (PAM) — Amebic Encephalitis.” Centers for Disease Control and Prevention. Accessed November 5-9, 2016. Web. <>.
4)    Heggie, Travis W. “Swimming with Death: Naegleria Fowleri Infections in Recreational Waters.” Travel Medicine and Infectious Disease 8.4 (2010): 201–206. Web.

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